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Discovery of Spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amines as Potent NOP and Opioid Receptor Agonists.
Schunk, Stefan; Linz, Klaus; Frormann, Sven; Hinze, Claudia; Oberbörsch, Stefan; Sundermann, Bernd; Zemolka, Saskia; Englberger, Werner; Germann, Tieno; Christoph, Thomas; Kögel, Babette-Y; Schröder, Wolfgang; Harlfinger, Stephanie; Saunders, Derek; Kless, Achim; Schick, Hans; Sonnenschein, Helmut.
Afiliação
  • Schunk S; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Linz K; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Frormann S; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Hinze C; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Oberbörsch S; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Sundermann B; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Zemolka S; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Englberger W; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Germann T; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Christoph T; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Kögel BY; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Schröder W; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Harlfinger S; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Saunders D; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Kless A; Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
  • Schick H; ASCA GmbH Angewandte Synthesechemie Adlershof , Magnusstr. 11, 12489 Berlin, Germany.
  • Sonnenschein H; ASCA GmbH Angewandte Synthesechemie Adlershof , Magnusstr. 11, 12489 Berlin, Germany.
ACS Med Chem Lett ; 5(8): 851-6, 2014 Aug 14.
Article em En | MEDLINE | ID: mdl-25147602
ABSTRACT
We report the discovery of spiro[cyclohexane-pyrano[3,4-b]indole]-amines, as functional nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonists with strong efficacy in preclinical models of acute and neuropathic pain. Utilizing 4-(dimethylamino)-4-phenylcyclo-hexanone 1 and tryptophol in an oxa-Pictet-Spengler reaction led to the formation of spiroether 2, representing a novel NOP and opioid peptide receptor agonistic chemotype. This finding initially stems from the systematic derivatization of 1, which resulted in alcohols 3-5, ethers 6 and 7, amines 8-10, 22-24, and 26-28, amides 11 and 25, and urea 12, many with low nanomolar binding affinities at the NOP and mu opioid peptide (MOP) receptors.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: ACS Med Chem Lett Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: ACS Med Chem Lett Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Alemanha